title: Dissolving polymer microneedle patches for rapid and efficient transdermal delivery of insulin to diabetic rats.
abstract: This study presents a dissolving microneedle patch, composed of starch and gelatin, for the rapid and efficient transdermal delivery of insulin. The microneedles completely dissolve after insertion into the skin for 5 min, quickly releasing their encapsulated payload into the skin. A histological examination shows that the microneedles have sufficient mechanical strength to be inserted in vitro into porcine skin to a depth of approximately 200 μm and in vivo into rat skin to 200-250 μm depth. This penetration depth does not induce notable skin irritation or pain sensation. To evaluate the feasibility of using these dissolving microneedles for diabetes treatment insulin-loaded microneedles were administered to diabetic rats using a homemade applicator. Pharmacodynamic and pharmacokinetic results show a similar hypoglycemic effect in rats receiving insulin-loaded microneedles and a subcutaneous injection of insulin. The relative pharmacological availability and relative bioavailability of insulin were both approximately 92%, demonstrating that insulin retains its pharmacological activity after encapsulation and release from the microneedles. Storage stability analysis confirms that more than 90% of the insulin remained in the microneedles even after storage at 25 or 37°C for 1 month. These results confirm that the proposed starch/gelatin microneedles enable stable encapsulation of bioactive molecules and have great potential for transdermal delivery of protein drugs in a relatively painless, rapid, and convenient manner.
authors.affiliation: Department of Chemical Engineering, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Ming-Hung
authors.initials: MH
authors.lastname: Ling
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Chen
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D009339:Needles; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000473:pathology
chemical_list: D001786:Blood Glucose; D003911:Dextrans; D007328:Insulin; D011108:Polymers; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate
keywords: Bioavailability; Bolus release; Hypoglycemic effect; Polysaccharide; Protein delivery